Document Detail

Modification of 1-substituents in the 2-azabicyclo[2.1.1]hexane ring system; approaches to potential nicotinic acetylcholine receptor ligands from 2,4-methanoproline derivatives.
MedLine Citation:
PMID:  14629156     Owner:  NLM     Status:  MEDLINE    
Successful nucleophilic substitution at a methylene attached to the bridgehead (1-) position of the 2-azabicyclo[2.1.1]hexane ring system opens the way to construction of novel derivatives having a wider range of functional groups attached to the 1-position via a methylene "spacer" (including the beta-amino acid homologue of 2,4-methanoproline) and provides access to epibatidine analogues containing heterocyclic substituents and also to further homologation at the 1-position. Displacements with loss of a nucleofuge (e.g., loss of mesylate anion from the 1-mesyloxymethyl derivative) require thermal activation but proceed without the rearrangement initially anticipated in such a strained bicyclic ring system. A novel tricyclic carbamate intermediate 17 has been isolated; nucleophilic attack on 17 leads directly to the isolation of N-deprotected substitution products (with concomitant decarboxylation).
John R Malpass; Anup B Patel; John W Davies; Sarah Y Fulford
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of organic chemistry     Volume:  68     ISSN:  0022-3263     ISO Abbreviation:  J. Org. Chem.     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2003-11-21     Completed Date:  2004-03-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985193R     Medline TA:  J Org Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9348-55     Citation Subset:  IM    
Department of Chemistry, University of Leicester, Leicester LE1 7RH, United Kingdom.
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MeSH Terms
Aza Compounds / chemical synthesis*,  chemistry
Bicyclo Compounds, Heterocyclic / chemical synthesis*,  chemistry
Models, Chemical
Molecular Structure
Nicotinic Agonists / chemical synthesis*,  chemistry
Proline / analogs & derivatives*,  chemistry*
Structure-Activity Relationship
Reg. No./Substance:
0/2,4-methanoproline; 0/Aza Compounds; 0/Bicyclo Compounds, Heterocyclic; 0/Ligands; 0/Nicotinic Agonists; 147-85-3/Proline

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